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CONDITIONS
AND DISEASES PREVENTED AND HELPED BY A LOW-CARB, HIGH-FAT DIET

Heated Starches and Cancer Risk

Summary - Acrylamide in Heat-Processed Foods

A scientific group at the University of Stockholm, headed by Prof. Margareta
Törnqvist, has found that acrylamide is formed during heating of
starch-rich foods to high temperatures.

Acrylamide is a "probable human carcinogen", according to international risk
assessments.

The Swedish National Food Administration has developed a new, rapid
LC/MS/MS-method for the analysis of acrylamide in foods. Analysis has shown
that acrylamide is present in a large number of foods, including many regarded
as staple foods. The levels of acrylamide differ widely within each food group
analysed.

Using information on the levels in different foods and Swedish food consumption
data, it seems reasonable to conclude that a significant number, perhaps
several hundred, of the annual cancer cases in Sweden can be attributed to
acrylamide. The risks associated with acrylamide in foods are not new - we have
probably been exposed to acrylamide in food for generations. The new, emerging
knowledge may make it possible to reduce the risks that we have so far accepted
without discussion. This is a very positive development.

Acrylamide in food is a global problem that requires international action. The
National Food Administration has therefore informed the European Commission,
other food safety agencies and international organisations about the findings.
It is important to obtain much more information through international
co-operation in research, in order to be able to reduce the risks associated
with acrylamide in foodstuffs.

Detailed studies on the levels of acrylamide in different foods, an extended
risk characterisation and knowledge of the mechanisms of formation are vital.
Possible specific risk groups in the population have to be identified.

Due to lack of data, it is not possible at present to issue detailed and
specific recommendations to consumers or to the food industry and trade.
However, since acrylamide is most probably formed during heating of starch-rich
foods to high temperatures, some preliminary general recommendations can be
made to the food industry and trade and to consumers.

Toxicological aspects of acrylamide

Acrylamide and polyacrylamide are used in the industry for the production of
plastics.

It has been supposed that the main exposure for acrylamide in the general
population has been through drinking water and tobacco smoking. The exposure
via drinking water is small and the EU has determined maximum levels of 0.1
microgram per liter water.

Recent analyses have indicated that the exposure to acrylamide is probably
considerably higher (for non-smokers) from consumption of certain foods that
have been heated.

Acrylamide is water soluble and is quickly absorbed in the digestive tract. The
excreation via the urine is fast and half of the acrylamide is cleared from the
body in a few hours.

The toxicological effects of acrylamide are well known. It causes DNA damage
and at high doses neurological and reproductive effects have been observed.
Glycidamide, a metabolite of acrylamide, binds to DNA and can cause genetic
damage. Prolonged exposure has induced tumours in rats, but cancer in man has
not been convincingly shown. The International Agency for Research on Cancer
(IARC) has classified acrylamide as a "probably carcinogenic to humans" (Group
2A).

Acrylamide has been shown to induce gene mutations in cultured animal cells and
also in animals treated in vivo. Thus it is assumed that exposure also to very
low doses of acrylamide increases the risk for mutation and cancer.

High doses of acrylamide have been applied in the toxicological studies, which
is an accepted practice. 25-50 mg per kg body weight is the lowest dose that
has been shown to increase the mutation frequency in mouse. Recent studies in
the laboratory of the Swedish Food Adminstration have shown that chromosome
aberrations are induced in mice at 10-20 times lower doses.

Among the acrylamide metabolites glycidamide is considered the most likely
candidate for causing genetic damage. Glycidamide has been found in mice and
rats, and also in humans exposed to acrylamide.

Neurological damage was observed when rats were given acrylamide in their
drinking water. The lowest effective dose was 2 mg/kg body weight and day, and
the highest no-effect dose was 0.5 mg/kg body weight and day. Also humans
exposed to high doses of acrylamide have shown neurological damage, e.g. some
workers occupied in the building of the tunnel at HallandsÃ¥sen. It is difficult
to assess the highest acrylamide dose in humans that does not cause
neurological effects (NOEL). The level is probably several times higher than
the average acrylamide intake from food.

Acrylamide - Cancer studies and comparisons of risk

Epidemiological studies in man have not shown a correlation between exposure to
acrylamide and increased cancer rate. These studies have been criticised
because the number of studied persons was too low considering the expected
effect.

Two long-term studies in rat have shown a substantial increase of tumours in
different organs when the animals were exposed to acrylamide in drinking water.
Similar studies have been made in mice. The lowest effective dose was 2 mg/kg
body weight and day .

In the studies with rat the increase of tumours was most evident in specific
organs, e.g. mammary gland, uterus, adrenal gland, scrotal mesothelium. In mice
there was an increase of lung and skin tunours. These cancer studies have been
used for the assessment of the risk of cancer in humans due to acrylamide
exposure.

It should be noted that the genotoxic studies have indicated that there is no
threshold value for the risk of cancer induced by acrylamide, i.e. there is no
dose of acrylamide so low that it does not increase the risk of cancer. In
making these assessments it is assumed that man and rat have the same
sensitivity for cancer induction by acrylamide.

The results of the risk assessments are somewhat different since they are based
on different mathematical models. By consumption of 1 microgram acrylamide/kg
body weight and day the lifetime risk for cancer has been calculated to

4.5 per 1000 (U.S. EPA)

0.7 per 1000 (WHO)

10 per 1000 (Granath et al. 1999, Stockholm University)

These figures for risk should be compared to the total lifetime risk for cancer
in Sweden, i.e. one person of three will have cancer during his/her life. For
mostly unknown reasons 45 000 Swedes get cancer every year (most cases at high
ages). It is assumed that a third of all cases of cancer, are due to the diet.
For comparison one can mention other assessments of lifetime cancer risks: 3
per 1000 for ionizing radiation (general background excluding radon), 0.01 per
1000 for aflatoxin (a fungus toxin found in e.g. peanuts) at the EU maximum
level, and this last figure is also representative for most carcinogens found
in food.

Acrylamide in foodstuffs, consumption and intake

When foodstuffs were analysed at the Swedish National Food Administration (NFA)
in Uppsala and at AnalyCen AB in LidkÃ¶ping it was found that some foodstuffs,
which had been heated, could contain relatively high levels of the substance
acrylamide. In total, more than 100 food samples have been analysed at the NFA.
The food survey comprised bread, pasta, rice, fish, sausages, meat (beef and
pork), biscuits, cookies, breakfast cereals and beer, etc as well as some
ready-made dishes such as pizza and products based on potatoes, maize and flour.

The levels of acrylamide vary considerably between single foodstuffs within
food groups, but potato crisps and French fries generally contained high levels
compared to many other food groups. The average content in potato crisps is
approximately 1000 mikrogram/kg and in French fries approximately 500
mikrogram/kg. Other food groups which may contain low as well as high levels of
acrylamide are crisp bread, breakfast cereals, fried potato products, biscuits,
cookies and snacks, e.g. popcorn.

Foodstuffs which are not fried, deep fried or oven-baked during production or
preparation are not considered to contain any appreciable levels of acrylamide.
No levels could be detected in any of the raw foodstuffs or foods cooked by
boiling investigated so far (potato, rice, pasta, flour and bacon).

According to the NFA food survey "Riksmaten 1997-98", which is based on
approximately 1200 individuals between the age of 17 to 70 who recorded their
food consumption during one week, an average intake of acrylamide of
approximately 25 mikrogram per day (maximum intake is approximately six times
higher) is obtained, based on the food groups shown below. The remaining food
groups are estimated to account for approximately 10-15 mikrogram of
acrylamide; in total an average intake of 35-40 mikrogram. The percentage
contribution based on an intake of 40 mikrogram akrylamid per day results in:

It should be emphasized that, considering our present knowledge, the
contribution from different food groups is extremely uncertain since only
foodstuffs which were expected to contain acrylamide have been examined so far.
There is also a considerable variation in the measured levels of acrylamide.

Young adults (17 to 34 years of age) have, according to "Riksmaten", a higher
consumption of snacks (nuts, chips and popcorn) than other adults. For children
under 17 years of age newer data are lacking. In the food survey "Ungdom mot Ã¥r
2000" (Samuelson et al 1996), which was carried out 1993-94 among 15-year olds
in Uppsala and TrollhÃ¤ttan, the consumption of snacks was comparable to that of
young adults in Riksmaten. Children have a lower average body weight than the
70 kg generelly assumed when carrying out risk assessments. This implies that
the food intake per kg body weight and the exposure to various substances could
be even larger for those groups of individuals compared to adults. According to
Riksmaten, 10 per cent of the adult population consumes 90 per cent of the
snacks consumed in Sweden.

An alternative way of estimating the intake of acrylamide is by adduct
measurement, that is to measure a reaction product of acrylamide with the
protein of the blood, the hemoglobin (TÃ¶rnqvist et al 1997). This reaction
product seems to occur in all investigated humans at approximately the same
levels and is furthermore a measurement of the continously administered dose of
acrylamide. The reason is unknown in this case, but workers who were exposed to
acrylamide at the tunnel accident at HallandsÃ¥sen in Sweden had higher levels
of this reaction product in their blood.

In the general population, although not in smokers (who have a level of this
adduct 2-3 times the background level), the background level has been estimated
to account for a daily intake corresponding to approximately 100 mikrogram per
day.

Other sources than foodstuffs (estimated average intake of 35-40
mikrogram/day), e.g. cosmetics, drinking water, and a possible endogenous
formation in the body of acrylamide, could, to a lower extent contribute to the
background level. Estimated administered amount of acrylamide for the formation
of the background level together with levels of acrylamide in foodstuffs are,
however, presently extremely uncertain.

Analytical methodology and survey results for
acrylamide in foods

Findings of a specific haemoglobin adduct of acrylamide
in human subjects, later also in rats fed with fried feed,
lead scientists at the University of Stockholm to the
discovery that acrylamide can be formed in foods during
cooking. At a later stage they also demonstrated high
acrylamide levels in some foodstuffs that were heated in
laboratory experiments.

Based of this information the SwedishNational Food
Administration decided to try to develop a new analytical
procedure for acrylamide detection in foods. One important
purpose was to enable verification of the presence of
acrylamide in food by using alternative methodology, i.e.
to confirm the identity of acrylamide and to show that it
was not formed as an artefact during the analytical
procedure. Moreover, there was a need for a simple and
fast method that could be used for extensive
investigations of acrylamide in a wide range of foods.

The development work,started in January 2002 and has
resulted in a new and significantly improved analytical
method. The procedure is presently under validation and
accreditation has been requested from the national
accreditation authority SWEDAC. The method utilizes liquid
chromatography coupled to two-stage mass spectrometry
(LC-MS-MS). This modern state-of-the-art technology is
considered highly reliable for chemical structure
identification. Quantification is aided by spiking each
sample prior to extraction with an internal standard
consisting of an acrylamide molecule where three of the
hydrogen atoms have been substituted by the isotope
deuterium.

As a complement to the research on acrylamide formation
at the University of Stockholm, the National Food
Administration has started a broad survey of acrylamide
levels in common foods. In order to speed up the
investigations, a number of samples were initially sent to
a private laboratory (AnalyCen AB, LidkÃ¶ping, Sweden),
also engaged by the University of Stockholm for acrylamide
analysis. The analytical method employed was a
modification of a procedure originally developed for
analysis of acrylamide in water. The major disadvantages
compared to the new method include a lower sample
throughput and the fact that it is based on indirect
detection of acrylamide through volatile derivative.

Up to this date more than a hundred food samples have
been collected by the National Food Administration and
analysed for acrylamide. No levels could be detected in
any of the raw foodstuffs or foods cooked by boiling
investigated so far (potato, rice, pasta, flour and
meat). A summary of the other results is given in Table
1. Various fried and oven-cooked foods based on meats and
flour respectively, corn crisps, muesli, as well as some
of the breakfast cereals and crisp breads, were in the
concentration interval up to 100 mg/kg.
French fries and other fried, deep fried or oven-baked
potato products, together with some crisp breads,
biscuits,
crackers and breakfast cereals, were in the interval
100-1000 mg/kg. About half of
the potato crisp samples were also in this group while the
levels above 1000 mg/kg were
detected in the remaining half.

Individual results for all tested samples are given in
Table 2 (link at the bottom of this page). It must be
emphasized that the concentration figures in most cases
refers only to one single randomly selected package of
each specific product. The uncertainty intervals given in
the table are statistical estimations of the random errors
of the analytical procedure only. Moreover the choice of
products within each group is far from complete.

Consequently we would like to stress that knowledge
that could provide guidance in consumers' choice between
different products and brands within a certain food type
is still lacking.

The primary objectives so far have been to provide
concentration data for intake estimations of acrylamide
from foods and to identify the most important food types.
The investigation is in full progress and more data will
be published when available.

We are convinced that information now presented by the
University of Stockholm and the Swedish National Food
Administration will initiate considerable research and
investigation activities at official institutions and food
industries world-wide. Further studies on the occurrence
and formation of acrylamide in foods will hopefully lead
to modifications of production methods and raw materials
that will eliminate or limit the formation of acrylamide
in foods.

Recommendations regarding acrylamide in food

The Swedish National Food Administration (NFA) and researchers from Stockholm
University have found that acrylamide is formed in many types of food
prepared/cooked at high temperatures. No acrylamide formation has been detected
in boiled foodstuffs. The NFA has informed the European Commission and other
international authorities and organisations about the findings in order to
initiate international collaboration in the handling of the problem. Moreover,
international initiatives to commence multidisciplinary research are urgently
needed, since it is very likely that there are ways of decreasing the formation
of acrylamide during the cooking process.

Present knowledge does not allow for a balanced analysis of risks and benefits
of staple foods containing acrylamide. The Swedish NFA can currently only issue
general advice regarding the risk management of acrylamide to the food industry
and consumers.

Manufacturers

Current knowledge suggests that acrylamide is formed in carbohydrate-rich foods
at high temperatures. It is probable that research into the mechanisms behind
this formation may lead to changes in food processing/cooking that will
decrease the formation of acrylamide. The Swedish NFA recommends the food
industry to investigate whether acrylamide is formed during the production of
their food products. If acrylamide is formed, the industry should determine the
levels in their products and initiate research to find measures to reduce the
concentrations as much as possible.

Acrylamide is probably formed in many types of food, many of which have not yet
been analysed. It is therefore not possible at present to say which types of
food pose the greatest problem. The amount to which the consumer is exposed is
governed both by the level of acrylamide in the food and the amount of the food
consumed. If eaten in large quantities, foods with low levels of acrylamide may
contribute substantially to the total exposure. Foods with high levels may
contribute less if the consumption is low. It is therefore not possible to give
detailed advice about proper measures for consumer protection. The NFA
recommends that wholesalers and retailers collaborate with the authorities and
the food industry in their efforts to find means to decrease the formation of
acrylamide in food.

Restaurants and consumers

Current research indicates that some simple measures may reduce the acrylamide
exposure of the consumer. Cigarette smoking is a source of acrylamide; exposure
can be reduced by refraining from smoking. Research on food indicates that more
acrylamide is formed at higher temperatures and longer cooking times during
frying, deep-frying, broiling and grilling. No acrylamide has been found in
boiled foodstuffs.

More knowledge is needed before the dietary advice issued by the NFA can be
changed. Currently the NFA advises the public to eat more fruit, vegetables,
cereal products and bread, and to reduce consumption of fat-rich products. From
a nutritional perspective, boiling is more advantageous than cooking at high
temperatures. Avoid burning food during frying, deep-frying, broiling and
grilling and do not eat burned food.

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